Methods for preparing 2'-deoxynucleosides for use as antiviral and antineoplastic agents are generally known in the art of pharmaceutical chemistry. Typically, the art teaches that 2'-deoxynucleosides may be prepared by first preparing a desired carbohydrate, independently preparing a desired base, and condensing the two components to form the desired product (see, e.g., U.S. Pat. No. 5,118,820).
More specifically, U.S. Pat. No. 4,965,374 ('374) discloses the preparation of protected 2,2-difluorolactone intermediates having up to two centers of chirality. One such intermediate having a chiral center consists of erythro and threo enantiomers of the formulae ##STR1## wherein P is a protecting group. The patent teaches the erythro enantiomer, which is preferred, because it provides a carbohydrate which has the stereochemistry of naturally occurring ribose. A carbohydrate having the stereochemistry of naturally occurring ribose is preferred because it provides final product nucleosides which exhibit superior biological activity.
A second intermediate, taught in the U.S. Pat. No. 4,965,374, possesses a third chiral center which is produced at the anomeric C-1 carbon atom when the carbonyl portion of the lactone is converted to the respective alcohol. The two resulting anomers for the desired erythro configuration are identified as .alpha. and .beta. anomers of the formulae ##STR2##
In this method of preparing 2,2-difluoronucleosides, the hydroxy group at the 1-position is ultimately replaced by a heterocyclic base such as cytosine to provide protected precursors to the biologically active 2'-deoxy-2',2'-difluoronucleosides. This .beta.-anomer precursor is preferred because it provides, after deprotection, 2'-deoxy-2',2'-difluoronucleosides which possess superior biological activity.
In expanding the art of 2'-deoxy-2',2'-difluoronucleoside preparation, the present invention provides novel intermediates which are useful for the preparation of 2'-deoxynucleosides having pharmacological activity. Also provided are convenient processes for the preparation of such novel intermediates and pharmacologically active compounds.